P16 HEALTH-RELATED QUALITY OF LIFE FOR FRAIL TRANSPLANT-INELIGIBLE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA TREATED WITH DARATUMUMAB, LENALIDOMIDE AND DEXAMETHASONE: SUBGROUP ANALYSIS OF MAIA TRIAL
Authors: T. Facon, T. Plesner, S. Usmani, S. Kumar, N. Bahlis, C. Hulin, R. Orlowski, H. Nahi, P. Mollee, K. Ramasamy, M. Roussel, A. Jaccard, M. Delforge, L. Karlin, B. Arnulf, A. Chari, H. Pei, N. Gupta, S. Kaila, K. Matt, K. Gries, R. Carson, F. Borgsten, K. Weisel, A. Perrot
Journal: HemaSphere (2023)

Introduction: In the primary analysis of the phase 3 MAIA trial (NCT02252172), daratumumab, lenalidomide and dexamethasone (D-Rd) improved progression-free survival (PFS) in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM) vs Rd. With longer follow-up (median: 56.2 months), D-Rd continued to demonstrate PFS benefit, conferred an overall survival benefit, induced deeper responses, and was associated with clinically meaningful improvements in patient-reported outcomes (PROs) vs Rd. The median age of these patients was 73 years with 43.6% of patients aged ≥75 years. Consistent with the overall population, in a frailty subgroup analysis (median age: 77 years), D-Rd also demonstrated deeper responses and PFS benefit vs Rd (not reached vs 30.4 months; HR, 0.62; P = 0.003) in frail patients at a median follow-up of 36.4 months. Although, D-Rd improved clinical outcomes in these elderly frail patients, little is known about health-related quality of life (HRQoL) outcomes. In frail patients, improving HRQoL and minimizing the risk of toxicity is paramount. Here, we assess PROs in the frail patients in the MAIA trial. Methods: Patients were randomized 1:1 to D-Rd or Rd until disease progression (PD) or unacceptable toxicity. Frailty was assessed using the simplified frailty score. PROs were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item. Questionnaires were completed at baseline, on day 1 of cycles 3, 6, 9, and 12 for year 1, and every 6 months thereafter until PD. Analyses were conducted on intent-to-treat patients. Treatment effect was assessed for change from baseline by a mixed-effects model for repeated measures. Meaningful thresholds for worsening were defined a priori based on published literature. Results: Overall, 737 patients were randomized; 341 patients were classified as frail (D-Rd, n=172; Rd, n=169). Over time, frail patients treated with D-Rd showed large reductions in pain from baseline (≥20-point change) and were greater with D-Rd than Rd. Fatigue symptoms were moderately reduced with both treatments. Increases in global health status (GHS) were consistent over time for both treatment groups. Patients treated with D-Rd showed improvements from baseline in physical functioning that were greater than Rd until cycle 42 and increases in emotional and social functioning were seen with both treatments that were numerically greater with D-Rd at several time points. Improvements in role functioning were seen with both treatments with no difference between treatments. No meaningful changes from baseline were observed in nausea and vomiting with either treatment. Median time to first worsening was longer with D-Rd than Rd for GHS. Median time to first worsening for the other functional (emotional, social, role) and symptom (nausea and vomiting) scales numerically favored D-Rd vs Rd, except cognitive functioning and fatigue. Median time to worsening of pain symptoms was not reached for D-Rd. Conclusions: Frail TIE patients with NDMM treated with D-Rd reported improvements in GHS (an overall HRQoL measure) and physical functioning, with a notable reduction in pain from baseline throughout the duration of therapy. D-Rd is not only clinically effective but also results in a sustained improvement in HRQoL for frail TIE patients with NDMM.